Investigations of a cytosolic receptor for 25-hydroxycholesterol will be aimed at determining its purification, its physical and chemical properties, the kinetics of ligand binding, its tissue distribution, and its relationship to cholesterol synthesis. A postulated role of 32-hydroxylanosterol in the regulation of cholesterol synthesis will be investigated with cultured cells. Alterations in the intracellular level of 32-hydroxylanosterol will be correlated with changes in the activity of HMG-CoA reductase. Studies of the effects of side chain-substituted sterols on membrane structure and functions will be continued. Genetic and biochemical studies of mutant cell lines resistant to 25-hydroxycholesterol will be carried out.